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Full disc observations of the Sun in the H$\alpha$ line provide information about the solar chromosphere and in particular about the filaments, which are dark and elongated features that lie along magnetic field polarity inversion lines. This makes them important for studies of solar magnetism. Since full disc H$\alpha$ observations have been performed at various sites since 1800s, with regular photographic data having started in the beginning of the 20th century, they are an invaluable source of information on past solar magnetism. In this work we aimed at deriving accurate information about filaments from historical and modern full disc H$\alpha$ observations. We have consistently processed observations from 15 H$\alpha$ archives spanning 1909-2022. Our data processing includes photometric calibration of the data stored on photographic plates. We have constructed also Carrington maps from the calibrated H$\alpha$ images. We find that filament areas are affected by the bandwidth of the observation. Thus, cross-calibration of the filament areas derived from different archives is needed. We have produced a composite of filament areas from individual archives by scaling all of them to the Meudon series. Our composite butterfly diagram shows very distinctly the common features of filament evolution, that is the poleward migration as well as a decrease in the mean latitude of filaments as the cycle progresses. We also find that during activity maxima, filaments on average cover about 1% of the solar surface. We see only a weak change in the amplitude of cycles in filament areas, in contrast to sunspot and plage areas. Analysis of H$\alpha$ data for archives with contemporaneous Ca II K observations allowed us to identify and verify archive inconsistencies, which will also have implications for reconstructions of past solar magnetism and irradiance from Ca II K data., Comment: 21 pages, 14 figures, accepted for publication in A&A

The ionospheric response at middle latitudes to geomagnetic storms is not yet very well understood. Total electron content (TEC) variations associated with eight strong geomagnetic storms between 2015 and 2022 obtained from GNSS receivers in the eastern area of the North Atlantic (Portuguese continental and insular territory) are studied in an attempt to fill this gap. It was found that for most of the studied geomagnetic storms, TEC variations are synchronous for the longitudinal ranges from 27° W and 9° W. In the southern part of the studied region (around 32° N), the amplitude of TEC variations is, in general, significantly higher than in the northern part (around 39° N). Some of the studied geomagnetic storms were associated with TEC variations that we interpret as effects of post-sunset equatorial plasma bubbles that travelled well north from their habitual region. Additionally, though most of the studied storms were accompanied by reports on different kinds of malfunction of GNSS systems (GPS; GALILEO and other), there is no clear pattern in their appearance in dependence on the geomagnetic/ionospheric storms’ strength, commencement time, and its characteristics, in general.

We present a magnetic flux rope (FR) extraction tool for solar coronal magnetic field modelling data, which builds upon the methodology from Wagner et al. (2023). We apply the scheme to magnetic field simulations of active regions AR12473 and AR11176. We compare the method to its predecessor and study the 3D movement of the newly extracted FRs up to heights of 200 and 300 Mm, respectively. The extraction method is based on the twist parameter and a variety of mathematical morphology algorithms, including the opening transform and the morphological gradient. We highlight the differences between the methods by investigating the circularity of the FRs in the plane we extract from. The simulations for the active regions are carried out with a time-dependent data-driven magnetofrictional model (TMFM; Pomoell et al. (2019)). We investigate the FR trajectories by tracking their apex throughout the full simulation time span. We demonstrate that this upgraded methodology provides the user with more tools and less a-priori assumptions about the FR shape that, in turn, leads to a more accurate set of field lines. The propagation analysis yields that the erupting FR from AR12473 showcases stronger dynamics than the AR11176 FR and a significant deflection during its ascent through the domain. The AR11176 FR appears more stable, though there still is a notable deflection. This confirms that at these low coronal heights, FRs do undergo significant changes in the direction of their propagation even for less dynamic cases. The modelling results are also verified with observations, with AR12473 being indeed dynamic and eruptive, while AR11176 only features an eruption outside of our simulation time window., Comment: Accepted for publication in Astronomy & Astrophysics

Studies and reconstructions of past solar activity require data on sunspots as well as faculae/plage and network. Such data are also important for understanding the magnetic activity and variability of the Sun and Sun-like stars. The longest available direct faculae/plage datasets are white-light facular and Ca II K observations going back to 1874 and 1892, respectively. Prior to that time, the only direct data available are for sunspots. We reassess the relationship between plage areas and sunspot records (areas and numbers) since 1892, to allow reconstructions of facular/plage areas which can be employed for studies going further back in time, i.e. over the period when solely sunspot observations are available. We use the plage areas derived from 38 consistently processed Ca II K archives as well as the plage area composite based on these archives. We find the relationship between plage and sunspot areas and numbers to be well represented by a power law function. We further find that the relationships depend on the bandwidth and the solar cycle strength. The reconstructions with a power law relationship are in good agreement with the original plage area series, whereas employment of a cycle-strength-dependent relationship improves the reconstructions only marginally. Performing the same analysis on other previously published plage area series, usually derived from a single archive with diverse processing techniques, returns different results when using different time series. This highlights the importance of applying a consistent processing to the various archives and demonstrates the uncertainties introduced by using previously published series. Our results have implications for past solar activity and irradiance reconstructions as well as for stellar activity studies, which sometimes assume a linear dependence between plage and sunspot areas., Comment: 22 pages, 13 figures, accepted for publication in Astronomy & Astrophysics

The present work aims to validate the positions of solar filaments published in the Annals of Coimbra University Astronomical Observatory, currently the Geophysical and Astronomical Observatory of the University of Coimbra, corresponding to years 1929 to 1941. The published Stonyhurst positions were obtained by an original method devised in the early 20th century that used a spherical calculator instrument, a wood-made model of the sun. We used the digital images of the original spectroheliograms to measure the positions of the filaments, and heliographic coordinates were determinate with the routines implemented on python package Sunpy. The correlation coefficients between both sets of coordinates are positive and highly significant. The results validate the method used at the Coimbra observatory and the data published. We conclude that Coimbra solar filaments catalogues are reliable and can therefore be considered for future solar activity studies., Comment: 19 pages, 10 figures, Accepted for publication on Solar Physics

The present work aims to validate the positions of solar filaments published in the Annals of Coimbra University Astronomical Observatory, currently the Geophysical and Astronomical Observatory of the University of Coimbra, corresponding to years 1929 to 1941. The published Stonyhurst positions were obtained by an original method devised in the early 20th century that used a spherical calculator instrument, a wood-made model of the Sun. We used the digital images of the original spectroheliograms to measure the positions of the filaments, and heliographic coordinates were determined with the routines implemented in the Python package Sunpy. The correlation coefficients between both sets of coordinates are positive and highly significant. The results validate the method used at the Coimbra observatory and the published data. We conclude that the Coimbra solar filament catalogues are reliable and can therefore be considered for future solar activity studies. © 2021, The Author(s), under exclusive licence to Springer Nature B.V.

Here we present datasets provided by a SCINDA GNSS receiver installed in the Lisbon airport area from November of 2014 to July of 2019. The installed equipment is a NovAtel EURO4 with a JAVAD Choke-Ring antenna. The data are in an archived format and include the general messages on quality of records (*.msg), RANGE files (*.rng), raw observables as the signal-to-noise (S/N) ratios, pseudoranges and phases (*.obs), receiver position information (*.psn), ionosphere scintillations monitor (ISMRB; *.ism) and ionospheric parameters: total electron content (TEC), rate of change of TEC index (ROTI), and the scintillation index S4 (*.scn). The presented data cover the full 2015 year. The raw data are of 1-minute resolution and available for each of the receiver-satellite pairs. The processing and the analysis of the ionosphere scintillation datasets can be done using a specific "SCINDA-Iono" toolbox for the MATLAB developed by T. Barlyaeva (2019) and available online via MathWorks File Exchange system. The toolbox calculates 1-hour means for ionospheric parameters for each of the available receiver-satellite pairs and averaged over all available satellites during the analyzed hour. Here we present the processed data for the following months in 2015: March, June, October, and December. The months were selected as containing most significant geomagnetic events of 2015. The 1-hour means for other months can be obtained from the raw data using the aforementioned toolbox. The provided datasets are interesting for the GNSS and ionosphere based scientific communities., Comment: arXiv admin note: text overlap with arXiv:1910.04044

We derive the plage area evolution over the last 12 solar cycles employing data from all Ca II K archives available publicly in digital form known to us, including several as yet unexplored Ca II K archives. We analyse more than 290,000 full-disc Ca II K observations from 43 datasets spanning the period 1892-2019. All images were consistently processed with an automatic procedure that performs the photometric calibration (if needed) and the limb-darkening compensation. The processing also accounts for artefacts plaguing many of the images, including some very specific artefacts such as bright arcs found in Kyoto and Yerkes data. We have produced a plage area time-series from each analysed dataset. We found that the differences between the plage areas derived from individual archives are mainly due to the differences in the central wavelength and the bandpass used to acquire the data at the various sites. We have empirically cross-calibrated and combined the results obtained from each dataset to produce a composite series of plage areas. "Backbone" series are used to bridge all the series together. We have also shown that the selection of the backbone series has little effect on the final plage area composite. We have quantified the uncertainty of determining the plage areas with our processing due to shifts in the central wavelength and found it to be less than 0.01 in fraction of the solar disc for the average conditions found on historical data. We also found the variable seeing conditions during the observations to slightly increase the plage areas during activity maxima. We provide the so far most complete time series of plage areas based on corrected and calibrated historical and modern Ca II K images. Consistent plage areas are now available on 88% of all days from 1892 onwards and on 98% from 1907 onwards., Comment: 23 pages, 19 figures, accepted for publication in A&A

Context. Studies of long-term solar activity and variability require knowledge of the past evolution of the solar surface magnetism. The archives of full-disc Ca II K observations that have been performed more or less regularly at various sites since 1892 can serve as an important source of such information. Aims. We derive the plage area evolution over the last 12 solar cycles by employing data from all Ca II K archives that are publicly available in digital form, including several as-yet-unexplored Ca II K archives. Methods. We analysed more than 290 000 full-disc Ca II K observations from 43 datasets spanning the period between 1892-2019. All images were consistently processed with an automatic procedure that performs the photometric calibration (if needed) and the limb-darkening compensation. The processing also accounts for artefacts affecting many of the images, including some very specific artefacts, such as bright arcs found in Kyoto and Yerkes data. Our employed methods have previously been tested and evaluated on synthetic data and found to be more accurate than other methods used in the literature to treat a subset of the data analysed here. Results. We produced a plage area time-series from each analysed dataset. We found that the differences between the plage areas derived from individual archives are mainly due to the differences in the central wavelength and the bandpass used to acquire the data at the various sites. We empirically cross-calibrated and combined the results obtained from each dataset to produce a composite series of plage areas. The 'backbone' approach was used to bridge the series together. We have also shown that the selection of the backbone series has little effect on the final composite of the plage area. We quantified the uncertainty of determining the plage areas with our processing due to shifts in the central wavelength and found it to be less than 0.01 in fraction of the solar disc for the average conditions found on historic

Here we present a "SCINDA-Iono" toolbox for the MATLAB. This is a software to analyze ionosphere scintillation indices provided by a SCINDA GNSS receiver. The toolbox is developed in the MATLAB R2018b. This software allows to preprocess the original data and analyze ionosphere scintillations on the 1-minute and 1-hour time scales both for averaged over all available satellites values and separately for each receiver-satellite pair., Comment: 11 pages, 7 figures

Background. Our aim was to assess the role of breast density on breast cancer mortality and recurrences, considering patient and tumour characteristics and the treatments received among women attending population-based screening programmes. Methods. We conducted a retrospective cohort study among women aged 50-69 years attending population-based screening programmes, diagnosed with invasive breast cancer between 2000 and 2009, and followed up to 2014. Breast density was categorised as low density (≤25% dense tissue), intermediate density (25-50%), and high density (≥50%). Cox proportional hazards regression models were fitted to estimate the adjusted hazard ratios (aHR) and 95% confidence intervals (95% CI) for death and recurrences, adjusting by patient characteristics, mode of detection (screen-detected vs. interval cancer), and tumour features. Results. The percentage of deaths and recurrences was higher among women with intermediate- and high-density breasts than among women with low-density breasts (p=0.011 for death; p=0.037 for recurrences). Adjusted Cox proportional hazards regression models revealed that women with intermediate- and high-density breasts had a higher risk of death than women with low-density breasts, being statistically significant for intermediate densities (aHR = 2.19 [95% CI: 1.16-4.13], aHR = 1.44 [95% CI: 0.67-3.1], respectively). No association was found between breast density and recurrences. Conclusions. Breast density was associated with a higher risk of death, but not of recurrences, among women participating in breast cancer screening. These findings reinforce the need to improve screening sensitivity among women with dense breasts and to routinely assess breast density, not only for its role as a risk factor for breast cancer but also for its potential influence on cancer prognosis.

Nuno Martinho,1–3 Liana C Silva,1,4 Helena F Florindo,1 Steve Brocchini,2 Mire Zloh,3 Teresa S Barata2 1Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal; 2Department of Pharmaceutics, UCL School of Pharmacy, London, 3School of Life and Medical Sciences, University of Hertfordshire, Hatfield, UK; 4Centro de Química-Física Molecular and IN – Institute of Nanoscience and Nanotechnology, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal Abstract: Dendrimers are hyperbranched polymers with a multifunctional architecture that can be tailored for the use in various biomedical applications. Peptide dendrimers are particularly relevant for drug delivery applications due to their versatility and safety profile. The overall lack of knowledge of their three-dimensional structure, conformational behavior and structure–activity relationship has slowed down their development. Fluorophores are often conjugated to dendrimers to study their interaction with biomolecules and provide information about their mechanism of action at the molecular level. However, these probes can change dendrimer surface properties and have a direct impact on their interactions with biomolecules and with lipid membranes. In this study, we have used computer-aided molecular design and molecular dynamics simulations to identify optimal topology of a poly(L-glutamic acid) (PG) backbone dendrimer that allows incorporation of fluorophores in the core with minimal availability for undesired interactions. Extensive all-atom molecular dynamic simulations with the CHARMM force field were carried out for different generations of PG dendrimers with the core modified with a fluorophore (nitrobenzoxadiazole and Oregon Green 488) and various surface groups (glutamic acid, lysine and tryptophan). Analysis of structural and topological features of all designed dendrimers provided

Intestinal pathogens use the host's excessive inflammatory cytokine response, designed to eliminate dangerous bacteria, to disrupt epithelial gut wall integrity and promote their tissue invasion. We sought to develop a non-antibiotic-based approach to prevent this injury. Molecular docking studies suggested that glycosylated dendrimers block the TLR4-MD-2-LPS complex, and a 13.6 kDa polyamidoamine (PAMAM) dendrimer glucosamine (DG) reduced the induction of human monocyte interleukin (IL)-6 by Gram-negative bacteria. In a rabbit model of shigellosis, PAMAM-DG prevented epithelial gut wall damage and intestinal villous destruction, reduced local IL-6 and IL-8 expression, and minimized bacterial invasion. Computational modelling studies identified a 3.3 kDa polypropyletherimine (PETIM)-DG as the smallest likely bioactive molecule. In human monocytes, high purity PETIM-DG potently inhibited Shigella Lipid A-induced IL-6 expression. In rabbits, PETIM-DG prevented Shigella-induced epithelial gut wall damage, reduced local IL-6 and IL-8 expression, and minimized bacterial invasion. There was no change in β-defensin, IL-10, interferon-β, transforming growth factor-β, CD3 or FoxP3 expression. Small and orally delivered DG could be useful for preventing gut wall tissue damage in a wide spectrum of infectious diarrhoeal diseases.

A set of 16 previously synthesized aryl-aminopyridine and aryl-aminoquinoline derivatives have been evaluated for cytotoxic activity against three cancer cell lines (human cervical cancer-HeLa; human chronic myeloid leukemia-K562; human melanoma-Fem-x) and two types of normal peripheral blood mononuclear cells, with and without phytohemaglutinin (PBMC - PHA; PBMC + PHA). Twelve of the studied compounds showed moderate cytotoxicity, with selectivity against K562 but not the remaining two cancer cell lines. Four compounds were not active in cytotoxicity assays, presumably due to high predicted lipophilicity and low solubility. To rationalize the observed cytotoxic effects, structure-based virtual screening was carried out against a pool of potential targets constructed using the inverse docking program Tarfisdock and bibliographical references. The putative targets were identified on the basis of the best correlation between docking scores and in vitro cytotoxicity. It is proposed that the mechanism of action of the studied aminopyridines involves the disruption of signaling pathways and cancer cell cycle through the inhibition of cyclin-dependent kinases and several tyrosine kinases, namely Bcr-Abl kinase and KIT receptor kinase. The obtained results can guide further structural modifications of the studied compounds aimed at developing selective agents targeting proteins involved in cancer cell survival and proliferation.